[unreadable] [unreadable] Chronic daily headache (CDH) is a neurological disorder characterized by >15 headache days per month and affects up to 4% of the general population. Most cases of CDH evolve from episodic headache. CDH patients often report chronic pericranial tenderness (allodynia) with episodes of increased headache pain. Both a long history of headache and a high frequency of headache attacks are risk factors for the progression of episodic to chronic headache. Little is known about the physiological mechanism for the transition from episodic headache to CDH. One theory is that the pain phase of migraine involves nociceptor activation on the dura due to neurogenic inflammation. According to this theory, recurrent headache patients experience repeated attacks of inflammation and nociceptor activation on the dura over time. The overall aim of this study is to assess the mechanism of the progression of episodic to chronic headache following repeated dural inflammation. Studies show that repeated nociceptor activation produces long-lasting changes in the peripheral trigeminal neurons and their central projections in the brain. This can increase the perception of pain in secondary or referred areas due to activity-dependent neuronal plasticity. We have developed a model of recurrent headache in rat where we can induce inflammatory stimulation on the dura at fixed intervals over weeks. Repeated, episodic infusion of inflammatory soup (IS) on the dura of rats models the episodic activation of the dura in patients with recurrent headache. We propose to investigate the electrophysiological and neurochemical factors important for the progression of episodic to chronic trigeminal pain using this model. We hypothesize that repeated inflammatory stimulation of the dura induces chronic long lasting changes in trigeminal sensory processing in our rat model of CDH. In order to test this hypothesis, we propose 3 specific aims. Aim 1 will test the hypothesis that there is a critical frequency of inflammatory stimulation of the dura that causes the transition to low trigeminal thresholds. Aim 2 will test the hypothesis that the transition to chronically low trigeminal thresholds induces a long lasting hyperresponsive state of the electrophysiological and neurochemical responses in the trigeminal nucleus caudalis. Aim 3 will test the hypothesis that clinical headache treatment strategies, that effectively block allodynia and sensitization in patients, with block the transition of rats from episodic to chronic trigeminal pain following recurrent inflammatory stimulation of the dura. Project Narrative Recurrent headache is the most common pain-related complaint and the seventh leading ailment seen in medical practice, accounting for 18 million physician visits each year. Chronic daily headache is a disorder that affects up to 4% of the general population. The overall aim of this study is to assess the mechanism of the progression of episodic to chronic headache following repeated dural inflammation. [unreadable] [unreadable] [unreadable]